title: Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture.
abstract: BACKGROUND
  Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS).
  
  
  METHODS
  Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC.
  
  
  RESULTS
  45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25%) and 6/100 (6%) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95% CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95% CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95% CI 1.02-1.08; p = 0.038).
  
  
  CONCLUSIONS
  Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.
authors.affiliation: Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD. U.S.A. tabibian.james@mayo.edu
authors.forename: James H
authors.initials: JH
authors.lastname: Tabibian
authors.forename: Mohit
authors.initials: M
authors.lastname: Girotra
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Yeh
authors.forename: Dorry L
authors.initials: DL
authors.lastname: Segev
authors.forename: Murat T
authors.initials: MT
authors.lastname: Gulsen
authors.forename: Guldane
authors.initials: G
authors.lastname: Cengiz-Seval
authors.forename: Vikesh K
authors.initials: VK
authors.lastname: Singh
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Cameron
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gurakar
mesh_terms: D000328:Adult; D000368:Aged; D000714:Anastomosis, Surgical; D015142:Baltimore; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000295:instrumentation; D002779:Cholestasis / Q000000981:diagnostic imaging / Q000209:etiology / Q000601:surgery*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012086:Reoperation; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects*; D015607:Stents; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus